Renal artery stenosis: atherosclerotic versus fibromuscular dysplasia

What renal artery stenosis is

Renal artery stenosis (RAS) is the narrowing of one or both renal arteries to a degree that compromises kidney perfusion. When narrowing is haemodynamically significant — typically at least 60% diameter reduction — it activates the renin-angiotensin-aldosterone system, producing renovascular hypertension. In bilateral or severe disease, progressive ischaemia damages the kidney parenchyma (ischaemic nephropathy), contributing to chronic kidney disease.

RAS accounts for roughly 1–5% of all hypertension cases but a higher proportion of resistant or secondary hypertension. Understanding it requires distinguishing two diseases that look similar on a scan but behave and respond to treatment completely differently.

A. Core clinical — the AU general practice framework

Two diseases, two completely different paths

Atherosclerotic RAS (approximately 90%) affects older patients (generally over 55), with a cluster of vascular risk factors — smoking, dyslipidaemia, diabetes, peripheral arterial disease, coronary artery disease, or cerebrovascular disease. The narrowing is at the ostium or proximal segment of the renal artery and is part of a systemic atherosclerotic process. Medical therapy is the mainstay. Two large trials — CORAL (Cooper, NEJM 2014) and ASTRAL (NEJM 2009) — demonstrated no benefit from routine renal artery stenting over optimal medical therapy.

Fibromuscular dysplasia (FMD, approximately 10%) is a non-inflammatory, non-atherosclerotic arteriopathy affecting mainly women aged 20–50. It produces the classical “string of beads” appearance of medial fibroplasia in the mid-to-distal renal artery. About 50% of patients have multifocal disease involving cervical, vertebral, and mesenteric arteries as well. Percutaneous transluminal renal angioplasty (PTRA) without stenting is first-line and achieves hypertension resolution or improvement in around 80–90% of cases.

Red flags that should trigger a secondary hypertension workup

The following features in a hypertensive patient warrant investigation for secondary causes including RAS:

• Hypertension onset before age 30 — strongly consider FMD in a young woman
• Hypertension onset after age 55 without prior hypertension history — atherosclerotic RAS
• Sudden worsening of previously well-controlled blood pressure
• Resistant hypertension — blood pressure above target despite three or more optimally dosed antihypertensives including a diuretic
• Unilateral small kidney on incidental imaging
• Creatinine rise exceeding 30% after starting an ACE inhibitor or ARB — highly suggestive of bilateral RAS or RAS in a solitary kidney; pause the drug and arrange imaging
• Recurrent flash pulmonary oedema with preserved left ventricular systolic function (Pickering syndrome) — bilateral RAS is the classic cause
• Abdominal or flank bruit on auscultation — specific but insensitive
• Atherosclerotic disease elsewhere — PAD, coronary artery disease, carotid disease

For FMD specifically, look for young hypertension in a woman, headache or pulsatile tinnitus, and a personal or family history of arterial dissection.

Investigation

First-line non-invasive:

• Renal artery duplex ultrasound — initial screen; non-invasive; operator-dependent; resistive index above 0.8 suggests parenchymal damage that may limit response to revascularisation
• CT angiography — high anatomical detail; iodinated contrast (caution in CKD)
• MR angiography — gadolinium contrast; avoid standard gadolinium if eGFR below 30 due to nephrogenic systemic fibrosis risk; newer gadolinium agents safer

Exclude other secondary causes in the same workup:

• Aldosterone-renin ratio for primary hyperaldosteronism
• 24-hour urinary or plasma metanephrines for phaeochromocytoma
• Dexamethasone suppression test if Cushing syndrome is suspected
• TSH, UEC, fasting glucose, lipid profile
• Urinalysis, urinary albumin/creatinine ratio

Definitive: Catheter renal angiography — gold standard, typically done at the time of planned intervention.

B. The evidence for medical therapy over stenting

CORAL and ASTRAL: no benefit from routine stenting

The CORAL trial (Cooper, NEJM 2014) randomised 947 patients with atherosclerotic RAS to stenting plus optimal medical therapy or optimal medical therapy alone. There was no significant difference in the composite primary endpoint (major cardiovascular or renal event), blood pressure reduction, or renal outcomes at median 43 months. ASTRAL (NEJM 2009) reached the same conclusion in 806 patients.

The clinical implication is clear: for most patients with atherosclerotic RAS, stenting adds procedural risk without improving outcomes. Revascularisation may still be appropriate in highly selected patients — see escalation section.

Optimal medical therapy for atherosclerotic RAS

Per eTG and the Heart Foundation of Australia:

1. ACE inhibitor or ARB — preferred for renovascular hypertension; monitor creatinine at one and four weeks after initiation; if creatinine rises over 30%, pause and arrange imaging for bilateral disease
2. Calcium channel blocker (amlodipine, nifedipine) — effective adjunct
3. Diuretic (thiazide or, in CKD, loop diuretic)
4. Spironolactone — excellent fourth-line for resistant hypertension (PATHWAY-2, Williams Lancet 2015); monitor potassium
5. High-intensity statin — standard for atherosclerotic cardiovascular disease
6. Low-dose aspirin (75–100 mg daily) — in established atherosclerotic disease
7. Lifestyle — smoking cessation, dietary salt restriction below 5 g daily, Mediterranean or DASH diet, regular aerobic exercise, alcohol moderation, weight management

Target blood pressure below 140/90 mmHg (general) or below 130/80 mmHg in higher-risk patients per the Heart Foundation 2016 guideline.

FMD: angioplasty first, no stenting needed

PTRA without stenting achieves sustained hypertension resolution in approximately 50–60% of FMD patients and improvement in a further 30–40%. Stenting is reserved for dissection complicating angioplasty or refractory restenosis.

After confirmed FMD:

• Screen cervical carotid and vertebral arteries (MRA or CTA minimum) — around half have multifocal disease
• Screen first-degree relatives if there is a family history
• Antiplatelet therapy (aspirin 75–100 mg daily)
• Pre-pregnancy planning and counselling — aneurysm and dissection risk; specialist obstetric input

C. Bilateral RAS and ACE inhibitor caution

Bilateral RAS or RAS in a solitary functioning kidney represents a special situation. ACE inhibitors and ARBs reduce intraglomerular pressure by dilating the efferent arteriole — in normal kidneys this is beneficial, but in a kidney solely dependent on angiotensin-II-mediated efferent tone to maintain glomerular filtration, withdrawing that tone precipitates acute kidney injury.

The 30% creatinine rise rule: if creatinine rises more than 30% after initiating an ACE inhibitor or ARB, pause the drug, arrange renal artery imaging promptly, and review with a nephrologist or vascular specialist.

D. Australian operations

MBS items

• Standard consults — 23/36/44
• Renal Doppler/duplex ultrasound — 55046/55047
• CT angiography — 56301/56307
• MR angiography — 63335/63336
• ECG — 11700
• GP Chronic Condition Management Plan — 965/967 for ongoing cardiovascular-renal shared care
• Echocardiogram — 55113 (specialist)

PBS

All standard antihypertensives (ACE inhibitors, ARBs, calcium channel blockers, thiazide and loop diuretics, spironolactone, beta-blockers), statins, and low-dose aspirin are PBS-listed.

Referral pathway

Setting	Referral
Suspected secondary HTN, investigation unremarkable	GP management; consider nephrology review if CKD coexists
Confirmed atherosclerotic RAS	Vascular nephrology or vascular surgery for shared management and revascularisation decision
Confirmed FMD	Interventional radiology or vascular surgery for PTRA; cervical vascular imaging
Bilateral RAS, creatinine deteriorating	Urgent nephrology and vascular surgery
Suspected phaeochromocytoma or Conn adenoma	Endocrinology

E. Special populations

Pregnancy. ACE inhibitors and ARBs are contraindicated in pregnancy due to fetotoxicity. Methyldopa, labetalol, and nifedipine are first-line for hypertension in pregnancy. Unrepaired symptomatic FMD carries aneurysm and dissection risk in pregnancy — specialist obstetric and vascular input is essential before conception.

Older patients with extensive atherosclerosis. Polypharmacy is common; careful review of medication interactions (NSAIDs blunting antihypertensive effect, potassium interactions with ACE inhibitors and spironolactone) and renal function monitoring are the GP’s most important contributions.

Young women with FMD. Many are diagnosed in the context of a first pregnancy or oral contraceptive prescription revealing new hypertension. Oral contraceptive pills raise blood pressure independently and are generally avoided in confirmed FMD; discuss alternative contraception. Referral to an FMD specialist or a unit with expertise in this condition gives the best long-term outcome.

When to escalate

Refer or discuss with vascular nephrology, vascular surgery, or interventional radiology when:

• Confirmed or high-probability RAS on imaging
• Creatinine rises above 30% after ACE inhibitor or ARB initiation
• Resistant hypertension not responding to three or more optimised agents plus a diuretic
• Recurrent flash pulmonary oedema
• Newly confirmed FMD — for cervical vascular imaging and angioplasty planning
• Deteriorating eGFR without alternative explanation in a patient with known or suspected renovascular disease

What this article is and is not

This is general health information drawn from Therapeutic Guidelines (eTG), the Heart Foundation of Australia, ESC/ESH 2024 Hypertension Guideline, and landmark trials including CORAL and ASTRAL. It is not personal medical advice and does not replace specialist vascular, nephrology, or interventional radiology input. Decisions about investigation, medication, and revascularisation are made in consultation with your own GP and specialist team.

For consumer resources: HealthDirect — High blood pressure, Better Health Channel, Heart Foundation.

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Sources cited

1. Therapeutic Guidelines (eTG) — Hypertension
2. Heart Foundation of Australia — Hypertension 2016
3. Cooper CJ et al. — CORAL trial (NEJM 2014)
4. ASTRAL Investigators — ASTRAL trial (NEJM 2009)
5. Williams B et al. — PATHWAY-2 trial (Lancet 2015)
6. Persu A et al. — ARCADIA FMD registry (Eur Heart J 2014)
7. Mancia G, Williams B — ESC/ESH 2024 Hypertension Guideline
8. KDIGO 2024 — Hypertension in CKD
9. HealthDirect — High blood pressure
10. Better Health Channel — High blood pressure